1. Field of the Invention
The present invention relates to systems, including methods and apparatus, for delivering therapy to specific sites in a living body. More particularly, the invention relates to implantable infusion systems for creating and maintaining microenvironments in a living body to provide therapeutic effects, including tissue regeneration and production of therapeutic agents for living tissue.
2. Description of Related Art
Microenvironments are spaces, either in vitro or in vivo, wherein specific conditions are controlled and maintained in order to obtain specific therapeutic effects, including, for example, the promotion of tissue regeneration and the introduction or fostering of growth and development of living cells that generate particular therapeutic agents. It is widely recognized that the tissues of the Central Nervous System (CNS) have much less capacity for regeneration than other tissues in the mammalian body. It has been suggested that the some tissues may lack cellular or substrate constituents that are conducive for growth during development (Liesi, 1985, EMBO J. 4:2505-2511; and Carbonetto et al, 1987, J. Neurosci. 7:610-620), or particular sites in the body may contain components which are nonpermissive inhibitory for cell regeneration (Schwab and Thoenen, 1985, J. Neurosci. 5:2415-2423). As a result, recent efforts have focused on the creation and maintenance of microenvironments to aid in the repair of damaged or degenerated area of the CNS. These efforts include, for example, the introduction of cells into the target site, and are described, for example, by Whittemore et al, xe2x80x9cGene Therapy and the Use of Stem Cells for Central Nervous System Regeneration,xe2x80x9d Advances in Neurology, Vol. 72, pp. 113-119 (1997); Will et al, xe2x80x9cRegeneration in Brain and Spinal Cord,xe2x80x9d Cellular and Molecular Basis of Regeneration From Invertebrates to Humans,xe2x80x9d pp. 379-397, Wiley and Sons (1998); and Stichel-Gunkel, xe2x80x9cThe Role of the Microenvironment in Axonal Regeneration,xe2x80x9d Advances in Anatomy, Embryology and Cell Biology 137, (1997). The entire writings of each of these references are incorporated herein by reference.
It is also known to utilize mechanical implements, such as nerve regeneration chambers, to define and maintain microenvironments in the immediate vicinity of a damaged nerve in the human body to foster the repair and growth of the damaged tissue. For example, U.S. Pat. No. 5,584,885, the entire writing of which is incorporated herein by reference, discloses a nerve regeneration chamber which maintains a microenvironment to promote the regeneration of a damaged nerve. The regeneration chamber includes injection ports and exhaust ports to supply agents to the regeneration chamber and to remove agents from the regeneration chamber. Such techniques require additional implantation and associated trauma in order to place the regeneration chamber at the target site.
It is further known, as exemplified in U.S. Pat. No. 5,832,932 to provide infusion systems for infusing therapeutic agents, in the form of drugs, to specific sites in the human brain to treat movement disorders and other diseases. However, known infusion therapy systems provide only a limited range of non-living substances to treat a target area of the living body and have not heretofore been used to create comprehensive microenvironments in a living body.
What is needed is an infusion system for delivering a carefully designed medicament composition for creating and maintaining a comprehensive microenvironment in a living body. Specifically, what is needed is an implantable infusion system capable of providing a diverse range of medicament compositions, including living and non-living substances, in order to create and maintain a desired microenvironment in a living body for an extended period of time.
The present invention solves the aforementioned problems by providing a system for infusing a carefully designed medicament composition to achieve a particular desired therapeutic effect. The composition may include living cells to treat a particular disease and which deliver exogenous substances to maintain a microenvironment in the living body. For example, stem cells may be provided in the composition to be introduced into the living body and, in an appropriate environment, caused to mature into nerve cells once delivered to a target site. The invention contemplates medicament compositions that include stem cells (neuro or otherwise), including homographs and allographs, adhesive peptides, substances which inhibit fiberblast growth, genetically modified cells which produce useful exogenous substances, nerve growth factor (NGF), and previously harvested cells from a living body. In another aspect, the invention contemplates the replication of cells in a reservoir, for example, to keep cells alive in a dormant state until infusion.
Still another aspect of the invention provides a particular treatment system for Parkinsonian patients in which stem cells are introduced into the living body and provided with other factors that encourage the cells to develop into dopamine-producing cells. Such cells are introduced into the existing cell structure, which is used as a framework for cell growth.
Yet another aspect of the invention provides a particular treatment system for patients who have experienced trauma to the CNS, where a carefully designed medicament composition is delivered to a gap in the nerve structure and newly introduced living cells fill the gap in an organized fashion providing a bridge for nerve impulses traversing the gap, restoring peripheral neural control of distal structures.
The unique advantages provided by the invention have application to the rebuilding or regeneration of tissue structures including nerves, bone, cartilage, tendons and organs. The prolonged infusion of a carefully designed composition operates to foster the development of tissue in cases, for example, where a living body has inadequate resources to provide for regeneration on its own. The invention is also advantageous in providing a comprehensive medicament composition including living cells and the substances required to sustain the life of those cells, to provide a microenvironment that produces therapeutic agents, such as dopamine in applications for treating Parkinsonian patients.